title: Short- and long-term efficacy of aspirin and clopidogrel for thromboprophylaxis for mechanical heart valves: an in vivo study in swine.
abstract: OBJECTIVE
  In the interest of exploring alternatives to warfarin, we tested the hypothesis that clopidogrel combined with aspirin is effective for thromboprophylaxis of mechanical valves using a swine model.
  
  
  METHODS
  Adult swine underwent heterotopic implantation of a modified bileaflet mechanical valved conduit bypassing the ligated, native descending thoracic aorta. Animals were randomized to no anticoagulation (n = 7), 175 U/kg dalteparin administered subcutaneously twice daily (n = 9), 325 mg of aspirin (n = 6), 75 mg of clopidogrel (n = 6), or 325 mg of aspirin and 75 mg of clopidogrel daily (n = 6) and survived for 30 days. Additionally, 11 animals were randomized to no anticoagulation (n = 5) or 325 mg of oral aspirin and 75 mg of clopidogrel daily (n = 6) and survived for 150 days.
  
  
  RESULTS
  At 30 days, we observed 216 +/- 270 mg of thrombus for the no anticoagulation group, 53 +/- 91 mg for the dalteparin group, 33 +/- 23 mg for the aspirin group, 25 +/- 10 mg for the clopidogrel group, and 17 +/- 9 mg for the combined aspirin and clopidogrel group, respectively (P < .01 for clopidogrel and aspirin vs no anticoagulation). At 150 days, we observed 223 +/- 200 mg of thrombus for the no anticoagulation group and 4 +/- 4 mg for the aspirin and clopidogrel group (P = .02). Mean platelet deposition on the valve was 4.1 x 10(9) +/- 3.6 x 10(9) for the no anticoagulation and 6.81 x 10(7) +/- 1.4 x 10(8) for the combined aspirin and clopidogrel groups, respectively (P = .03). No major hemorrhagic events were observed.
  
  
  CONCLUSIONS
  Effective short- and long-term thromboprophylaxis of mechanical valves can be achieved by using dual-antiplatelet therapy in this porcine model. Prospective human trials should be conducted with combination aspirin and clopidogrel as an alternative to warfarin in patients with bileaflet mechanical aortic valves.
authors.affiliation: Division of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: McKellar
authors.forename: Jess L
authors.initials: JL
authors.lastname: Thompson
authors.forename: Raul F
authors.initials: RF
authors.lastname: Garcia-Rinaldi
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Macdonald
authors.forename: Thoralf M
authors.initials: TM
authors.lastname: Sundt
authors.forename: Hartzell V
authors.initials: HV
authors.lastname: Schaff
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001705:Bioprosthesis; D000077144:Clopidogrel; D017985:Dalteparin / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects / Q000379:methods*; D007279:Injections, Subcutaneous; D011182:Postoperative Care; D011183:Postoperative Complications / Q000517:prevention & control; D011897:Random Allocation; D012307:Risk Factors; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D015996:Survival Rate; D013552:Swine; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control*; D015912:Thrombolytic Therapy / Q000379:methods; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors
chemical_list: D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin; D017985:Dalteparin